Target: endothelin pathway | | | | | | | | |
Ambrisentan | Galiè [36] | versus placebo | 202 ARIES-1 | I (2%)# II (38%)# III (55%)# IV (5%)# | SF-36 | 12 | Physical functioning | 0.005¶ |
192 ARIES-2 |
Bosentan | Galiè [60] | versus placebo (+/- sildenafil) | 185 | II (100%)# | SF-36 | 24 | Health transition index | 0.0244+ |
Macitentan | Mehta [73] | versus placebo (+/-PDE5i or prostanoid) | 742 | I (<1%)# II (52%)# III (46%)# IV (2%)# | SF-36v2 | 6 months | PCS, MCS and in seven out of eight domains | <0.05§ |
EOT | PCS | 3 mg 0.008ƒ 10 mg 0.001## |
MCS | 3 mg 0.085¶¶ 10 mg 0.053++ |
Target: nitric oxide pathway | | | | | | | | |
Riociguat | Ghofrani [74] | versus placebo (+/- prostanoid or ERA) | 443 | I (3%)# II (42%)# III (53%)# IV (1%)# Missing (<1%) | EQ-5D§§ | 12 (+4) | No significant improvement | 0.07 |
LPHƒƒ | Nominal improvement seen versus placebo | 0.002 |
Sildenafil | Pepke-Zaba [75] | versus placebo (+ background therapy) | 278 | I (<1%)# II (39%)# III (58%)# IV (3%)# | SF-36 | 12 | Physical function General health Vitality | <0.001 <0.001 <0.05 |
EQ-5D | Utility index Current health status | <0.01 |
Sastry [76] | versus placebo | 22 | II (82%) III (18%) | CHFQ | 6 | Dyspnoea Fatigue Emotional function | 0.009 0.04 0.06 |
Simonneau [77] | versus placebo (+ epoprostenol) | 267 | I (1%)# II (25%)# III (66%)# IV (6%)# Missing (2%) | SF-36v1 | 16 | Physical function Physical role General health Vitality Social functioning Mental health | 0.003 0.02 <0.001 <0.001 0.049 0.001 |
Tadalafil | Pepke-Zaba [78] | versus placebo (+/- bosentan) | 405 | I (1%)# II (32%)# III (65%)# IV (2%)# | SF-36 | 16 | Physical function### Role physical Bodily pain General health Vitality### Social function### | <0.01¶¶¶ <0.01### <0.01### <0.01### <0.01### <0.001### |
EQ-5D | EQ-5D VAS EQ-5D UK utility | 0.05 0.0001 |
Target: prostacyclin pathway | | | | | | | | |
Beraprost | Barst [57] | versus placebo | 116 | II (53%)# III (47%)# | MLHFQ | | No improvement shown | ns/data not shown |
Epoprostenol | Barst [34] | versus conventional therapy | 81 | III (74%) IV (26%) | CHFQ | 12 | Dyspnoea Fatigue Emotional function Mastery | +++ p<0.01 |
NHP | Emotional reaction Sleep |
Dyspnoea-fatigue rating | |
Iloprost (inhaled) | Olschewski [38] | versus placebo | 203 | III (59%) IV (41%) | EQ-5D | 12 | EQ-5D VAS | 0.026§§§ |
SF-12 | No improvement shown | ns |
Treprostinil | McLaughlin [61] | versus placebo (+ bosentan or sildenafil) | 235 | III (98%) IV (2%) | MLHFQ | 12 | Global score Physical score | 0.027ƒƒƒ 0.037 |